Advanced

Global Optogenetic Activation of Inhibitory Interneurons during Epileptiform Activity.

Ledri, Marco LU ; Grönning Madsen, Marita LU ; Nikitidou, Litsa LU ; Kirik, Deniz LU and Kokaia, Merab LU (2014) In Journal of Neuroscience 34(9). p.3364-3377
Abstract
Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. In particular, the possibility to specifically activate by light-determined interneuron populations expressing channelrhodopsin-2 provides an unprecedented opportunity of exploring their contribution to physiological and pathological network activity. There are several subclasses of interneurons in cortical areas with different functional connectivity to the principal neurons (e.g., targeting their perisomatic or dendritic compartments). Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or... (More)
Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. In particular, the possibility to specifically activate by light-determined interneuron populations expressing channelrhodopsin-2 provides an unprecedented opportunity of exploring their contribution to physiological and pathological network activity. There are several subclasses of interneurons in cortical areas with different functional connectivity to the principal neurons (e.g., targeting their perisomatic or dendritic compartments). Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices. Here we demonstrate that such approach results in a brief initial action potential discharge in CA3 pyramidal neurons, followed by prolonged suppression of ongoing epileptiform activity during light exposure. Such sequence of events was caused by massive light-induced release of GABA from ChR2-expressing interneurons. The inhibition of epileptiform activity was less pronounced if only parvalbumin- or somatostatin-expressing interneurons were activated by light. Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neuroscience
volume
34
issue
9
pages
3364 - 3377
publisher
Society for Neuroscience
external identifiers
  • pmid:24573293
  • wos:000332034700023
  • scopus:84894436158
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2734-13.2014
language
English
LU publication?
yes
id
4691ce56-a1eb-45f8-901a-bcf9027ea64f (old id 4333895)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24573293?dopt=Abstract
date added to LUP
2014-03-05 18:02:41
date last changed
2017-10-29 03:09:40
@article{4691ce56-a1eb-45f8-901a-bcf9027ea64f,
  abstract     = {Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. In particular, the possibility to specifically activate by light-determined interneuron populations expressing channelrhodopsin-2 provides an unprecedented opportunity of exploring their contribution to physiological and pathological network activity. There are several subclasses of interneurons in cortical areas with different functional connectivity to the principal neurons (e.g., targeting their perisomatic or dendritic compartments). Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices. Here we demonstrate that such approach results in a brief initial action potential discharge in CA3 pyramidal neurons, followed by prolonged suppression of ongoing epileptiform activity during light exposure. Such sequence of events was caused by massive light-induced release of GABA from ChR2-expressing interneurons. The inhibition of epileptiform activity was less pronounced if only parvalbumin- or somatostatin-expressing interneurons were activated by light. Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration.},
  author       = {Ledri, Marco and Grönning Madsen, Marita and Nikitidou, Litsa and Kirik, Deniz and Kokaia, Merab},
  issn         = {1529-2401},
  language     = {eng},
  number       = {9},
  pages        = {3364--3377},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {Global Optogenetic Activation of Inhibitory Interneurons during Epileptiform Activity.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.2734-13.2014},
  volume       = {34},
  year         = {2014},
}